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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 505 records · Page 28Linked to original sources
PubMed1991

Different gene loci for hyperkalemic and hypokalemic periodic paralysis.

The periodic paralyses are dominantly inherited disorders in which patients acutely develop muscle weakness in association with changes in the level of blood potassium. We recently reported genetic linkage of hyperkalemic periodic paralysis (HIKPP) to the gene encoding the adult form of the skeletal muscle sodium channel on the long arm of chromosome 17. In this paper, we exclude genetic linkage between hypokalemic periodic paralysis (HOKPP) and this sodium channel gene, demonstrating that there is non-allelic genetic heterogeneity among different forms of periodic paralysis. Electrophysiological abnormalities in muscle sodium conductance have been reported for both HIKPP and HOKPP as well as other muscle disorders characterized by membrane hyperexcitability or myotonia (myotonia congenita, paramyotonia congenita and the Schwartz-Jampel syndrome). The possibility that there may be a family of human muscle diseases arising from mutations in the sodium channel suggests these disorders may be classified by categories of mutations within this critical voltage-sensitive membrane protein.

Chromosome Mapping↗
PubMed1991

Ceftriaxone in treatment of serious infections. Pneumonia and lower respiratory tract infections.

One gram once daily of ceftriaxone is as effective as 2 gm for the common causative organisms of community-acquired and nosocomial pneumonias. It should not be used alone against L. pneumophila, the TWAR pneumoniae, and possibly anaerobic pathogens. Preliminary study suggests that a regimen of 500 mg a day may be effective in selected patients with simple pneumonias caused by sensitive pathogens. Ceftriaxone is safe, well tolerated, and cost-effective, which means it can play a significant therapeutic role in nursing homes and other long-term care facilities as well as in outpatient therapy.

Bacterial Infections↗
PubMed1991

The effect of a glaucoma medication reminder cap on patient compliance and intraocular pressure.

A multi-site, open-labeled clinical trial was conducted to evaluate the ease of use and acceptance of a newly developed medication cap with a memory aid (C Cap Compliance Cap, Allergan, Inc.) and its effect on patient compliance and intraocular pressure. One-hundred-twenty-two patients with glaucoma or ocular hypertension received their prescribed eye drops in bottles with the compliance cap. Overall, 83% of the patients found the compliance cap very easy to use. By the end of the study, significantly more patients (67%) claimed 100% compliance than prior to using the compliance cap (41%). An overall drop in intraocular pressure of 0.8 mm Hg was seen. However, in a subset of patients who reported an increase in compliance, mean intraocular pressure decreased from baseline by 1.7 mm Hg. The results of this study suggest that the compliance cap helps patients with glaucoma or ocular hypertension remember to take their medication as prescribed.

Adolescent↗
PubMed1991

Transactivation of heterologous promoters by HIV-1 tat.

To determine whether HIV-1 tat can transactivate a heterologous promoter lacking HIV sequences other than the TAR element, TAR was placed downstream of the chicken beta-actin promoter. Tat increased expression directed by the actin-TAR promoter to a degree equal to tat induction of the HIV-1 LTR. Optimal transactivation was observed when TAR was positioned downstream of the actin promoter such that the expected cap site of transcripts from this promoter would be the same as in transcripts directed by the HIV-1 LTR. Tat was able to transactivate, though to a lesser extent, a promoter consisting solely of a TATA element fused to TAR. Thus, tat induction does not require HIV-1 LTR promoter sequences other than TAR. Tat, when fused to the DNA binding domain of BPV-1 E2, was able to transactivate a truncated SV40 promoter containing upstream E2 binding sites, indicating that tat may be capable of transactivation when directed by a DNA binding protein to an upstream site in a heterologous promoter lacking all HIV sequences. Substitution of Ala for Lys at position 41 of tat in the tat-E2 fusion, a mutation which dramatically decreases tat transactivation of the HIV-1 LTR, eliminated this transactivation.

3T3 Cells↗
PubMed1991

Self-inflicted eye injuries.

Five cases of self-inflicted eye injury are described and discussed. A review of the literature shows that several psychiatric diagnoses have been assigned to people who damage their eyes. A variety of mechanisms to explain this phenomenon are described.

Adult↗
PubMed1991

Islet cell responses to glucose in human transplanted pancreas.

Postsurgery, pancreas transplantation results in alterations of carbohydrate metabolism. Additionally, immunosuppressive therapy impacts on glucose regulation. We evaluated the hormonal and metabolic responses of pancreas allografts, utilizing the hyperglycemic clamp technique coupled with the tritiated glucose methodology, in 11 volunteers who had received simultaneous pancreas-kidney transplantation (P-K) with systemic drainage. Their responses were compared with seven volunteers who had received only a kidney (K) graft and with seven normal control (C) volunteers. Although basal glucose and hepatic glucose output were similar in all three groups, basal insulin, C-peptide, glucagon, and pancreatic polypeptide were highest in the P-K group and lowest in normal subjects. During hyperglycemia, all groups showed a similar characteristic, initial complete suppression of hepatic glucose production, with recovery followed by a later suppression. Peripheral glucose uptake was similar in P-K and C subjects but decreased in K patients. Systemic insulin levels were fourfold higher in the pancreas transplant patients than in healthy subjects. Thus, under basal and hyperglycemic stimulation, 1) hepatic glucose homeostasis is regulated normally, even with pancreatic drainage into the systemic circulation; 2) overall glucose disposal is normal in P-K patients because of marked hyperinsulinemia; and 3) there is loss of tonic inhibition of endocrine pancreatic function secondary to pancreatic denervation.

Adolescent↗
PubMed1991

Once-daily ceftriaxone in the treatment of lower respiratory tract infections.

We conducted a retrospective clinical evaluation to assess the efficacy of a 1-gram once-daily regimen of intravenously administered ceftriaxone in the treatment of a variety of bacterial infections. Of the 250 patients studied, 167 had infections of the lower respiratory tract, approximately 70% of which were diagnosed as community-acquired pneumonias. The principal identified pathogens were Staphylococcus aureus and Haemophilus influenzae. Forty per cent of community-acquired pneumonias occurred in patients over 69 years of age, who showed a 13% mortality compared to a mortality rate of 4% in younger patients. Once-daily ceftriaxone was effective and well tolerated as empiric therapy for pneumonia likely to be caused by susceptible organisms.

Aged↗
PubMed1991

Bronchial mucus hypersecretion in acute quadriplegia. Macromolecular yields and glycoconjugate composition.

In acute quadriplegia we have noted that about one in five patients develops unexplained production of markedly excessive and tenacious bronchial mucus. Spontaneous recovery from mucus hypersecretion usually occurs within weeks to months. Mucus samples collected from 12 patients have been found to be abnormal. Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical ultracentrifuge analysis showed the mucus to contain considerable epithelial glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate compositions were characteristic of the GP from hypersecretory bronchial mucus such as in chronic bronchitis and cystic fibrosis. In five patients studied after recovery from hypersecretion, there tended to be relatively less GP. The mucus samples contained a high density glycoconjugate (GC): this had sugars of GP but also reacted positively with a monoclonal antibody to keratan sulfate. Its amino acid composition was different from that of GP: threonine was lower and glycine was higher than in GP. In mucus from one patient who died, chondroitin sulfate ABC and hyaluronic acid were identified as well. This suggests proteoglycans are involved in the pathophysiology of mucus hypersecretion. The sudden onset and spontaneous recovery of hypersecretion suggests that it is not due to gland hypertrophy. We speculate that in acute quadriplegia it is due to disturbed neuronal control of bronchial mucus gland secretion, perhaps related to initial disappearance and later reappearance of peripheral sympathetic nervous system tone.

Acute Disease↗
PubMed1991

Renal artery imaging: a prospective comparison of intra-arterial digital subtraction angiography with conventional angiography.

This study describes a systematic comparison of intra-arterial digital subtraction angiography (DSA) of the main renal arteries with conventional angiography (CA), the currently accepted "gold standard" for the diagnosis of renal artery stenosis. Twenty-five patients scheduled for abdominal aortography for various indications underwent first DSA then CA. The DSA and CA images were evaluated for number of renal arteries, presence and grade of renal artery stenosis, presence of post-stenotic dilation or fibromuscular changes, and diagnostic and pictorial adequacy of the images. DSA was found to be diagnostically adequate in 92% of cases, compared with 96% for CA. In evaluating significant main renal artery stenosis, which the authors assumed to be any stenosis greater than 50%, there were 10 such stenoses seen by CA. DSA also detected 10 cases, but there was 1 false positive and 1 false negative, yielding a sensitivity of 90% and a specificity of 98%. There was also close correlation of DSA and CA for the few cases of post-stenotic dilatation and fibromuscular dysplasia encountered. The authors conclude that DSA is an acceptable substitute for CA in the evaluation of patients for main renal artery stenosis.

Angiography↗
PubMed1991

Identification and expression of a regeneration-specific homeobox gene in the newt limb blastema.

Adult urodele amphibians are able to regenerate their limbs through the formation of a blastema, a growth zone of undifferentiated mesenchymal cells that arises locally at the plane of amputation. In an effort to define genes involved in pattern formation by the blastema, we isolated from a newt forelimb blastema library cDNA clones that identify a homeobox gene termed NvHbox 2. The amino acid sequence of the homeodomain is identical to that of the recently identified human HOX-4f gene (Acampora et al. 1989) and of the mouse Hox-5.5 (Dolle et al. 1989). NvHbox 2 is expressed in the limb blastema as a transcript of 3.4 kb that is not detectable in the normal limb. Analysis by RNAase protection demonstrates expression in limb and tail blastemas, but not in any of the adult tissues or organs tested. In the limb blastema NvHbox 2 was expressed in mesenchymal but not epithelial tissue. When matched and normalised samples of RNA from proximal (mid-humerus) and distal forelimb (mid-radius) blastemas were compared, the level of expression of NvHbox 2 was found to be 3- to 5-fold higher proximally. At two time points after injection of a proximalising dose of retinoic acid, the level of expression in a distal blastema was not increased in comparison to controls.

Amino Acid Sequence↗
PubMed1991

A newt type II keratin restricted to normal and regenerating limbs and tails is responsive to retinoic acid.

In order to understand the molecular mechanisms underlying the regenerative ability of the urodele limb, it is important to identify regeneration-associated proteins and to study their regulation. We have recently shown that the anti-cytokeratin monoclonal antibody LP1K reacts strongly with newt blastemal cells, while its reactivity is restricted in normal limbs. By screening a cDNA expression library from the newt blastema with LP1K, we have identified cDNA clones coding for a type II keratin (NvKII) expressed both in the mesenchyme and the specialized wound epithelium of the blastema. While the rod domain of the protein is highly conserved, the homology between NvKII and mammalian type II keratins drops markedly at the N- and C-terminal regions. The expression of this keratin was analysed by Northern blotting and RNAase protection analysis of various newt tissues, and appears to be organ specific, since it is restricted to normal and regenerating limbs and tails. In particular, we have investigated the expression of this keratin mRNA in normal and regenerating limbs. The transcript is barely detectable in the proximal portion of the normal limb, but its level is high in the distal one. After amputation, NvKII mRNA is expressed both in proximal and distal blastemas, although at higher levels distally, indicating that this keratin is regeneration associated. The NvKII transcript is detectable both in mesenchyme and in the wound epithelium of the regenerate, while no transcript is detectable in normal epidermis. The level of NvKII mRNA is markedly down-regulated both in normal and regenerating limbs following intraperitoneal injection with retinoic acid, a putative endogenous morphogen in limb regeneration.

Amino Acid Sequence↗
PubMed1990

Bone marrow transplantation: a review of a programme and its first 100 patients.

We review the first 100 patients receiving a bone marrow transplant as definitive therapy for their underlying disease. These patients were treated between May 1975 and June 1988. Median age was 8 years (range, 1 month to 43 years). Initially, patients were given transplants late in their disease but, as the programme progressed, patients were given transplants earlier and while in remission from their disease. The types of disease considered for treatment by bone marrow transplantation (BMT) expanded from leukaemia, and aplastic anaemia to include neuroblastoma, thalassaemia and immune deficiency. Initially matched donors were used but the source of marrow broadened to include mismatched family members, matched unrelated donors and autologous marrow. Problems after BMT were rejection (11%), acute graft-versus-host disease (GVHD) (45%), interstitial pneumonitis (22%) and relapse (36%). Recurrence of disease was the cause of half the deaths. GVHD was less frequent with the use of methotrexate and cyclosporin, T-cell depleted marrow or matched donors. Interstitial pneumonitis was more commonly associated with the use of mismatched donors and the development of GHVD. Relapse was less likely when BMT was undertaken in the first remission. At least one long-term side effect was seen in all patients treated with total body irradiation whereas no patient treated without irradiation had long-term side effects. The rate of disease free survival of patients at 24 months was 56% for matched, 48% for closely matched, 46% for autologous and 29% for mismatched transplants. For matched transplants mortality within the first 6 months after transplantation decreased from 28% before 1984 to 5% since 1984. Fifty-one patients have survived to June 1989, 49 of them disease free, for periods ranging from 12 to 123 months (median 29 months).

Adolescent↗
PubMed1990

Effects of novel bile salts on cholesterol metabolism in rats and guinea-pigs.

Novel bile salts (quaternary ammonium conjugates) inhibited cholic acid binding and transport in everted ileal sacs in vitro. The cationic piperazine conjugate of lithocholic acid (di-iodide salt, compound 8, BRL 39924A) appeared most active, inhibiting binding by 29% and transport by 59% in guinea-pig ileum (200 microM). BRL 39924A also inhibited taurocholate uptake into guinea-pig ileal sacs and cholate uptake into rat ileal sacs and was selected for further study in vivo. In hyperlipidaemic rats, BRL 39924A significantly raised cholesterol 7 alpha-hydroxylase activity and decreased hepatic accumulation of exogenous cholic acid. HDL cholesterol concentration in the serum increased and the level of VLDL plus LDL cholesterol decreased. In hyperlipidaemic guinea-pigs. BRL 39924A lowered serum total cholesterol and triglyceride levels. Although metabolic changes were less than those achieved with the bile acid sequestrant, cholestyramine, the doses of BRL 39924A used were much lower (100-500 mg/kg body wt). Selective inhibition of receptor mediated bile acid uptake may be associated with local side-effects but these novel bile salts are useful pharmacological tools to examine the effects of receptor blockade on lipoprotein metabolism.

Animals↗